Approximately 170 million people are infected with hepatitis C virus (HCV) world-wide. Current therapies are helpful, but are not effective in every patient. Moreover, many of the current therapies result in unwanted side-effects.
HCV particles attach and enter target cells through interactions between their viral glycoproteins E1 and E2 and cell surface receptor molecules. The viral entry step has been difficult to study because there is no reliable, easy to detect system for performing HCV/tissue culture infection. Hsu et al. (Proc. Natl. Acad. Sci. USA. 100(12):7271-7276 (2003)) and Bartosch et al. (J. Exp. Med. 197(5):633-42 (2003)) reported the generation of HCV pseudoparticles that use the core proteins of HIV-1 and authentic HCV E1 and E2 proteins. The pseudoparticles specifically infect hepatocytes and liver-derived cell lines. Such pseudoparticle infection can be neutralized by HCV patient serum as well as antibodies against E1 and E2 glycoproteins. CD81 is a host cell protein required, but not sufficient, for HCV pseudoparticle entry.
Peptides derived from HIV-1 envelope glycoproteins can bind HIV-1 and inhibit infection at the cell fusion step (Baldwin et al., Curr. Med. Chem. 10(17): 1633-1642 (2003)). Foung et al. (U.S. Pat. No. 6,692,908) discuss use of antibodies which inhibit HCV E1 and E1 binding to CD81 for treatment of HCV infection. Garry et al. (WO 2004/044220) discuss use of the peptides from the E1 envelope glycoprotein of hepaciviruses and E2 envelope glycoprotein of pestiviruses for treatment of viral infection. Furthermore, VanCompernolle et al. disclose imidazole-based small molecules that inhibit E2/CD81 binding (Virology 314(1):371-380 (2003)).
As mentioned above, in spite of the current availability of treatments for HCV, infections in many patients are not responsive. There remains a need in the art for additional treatments to the prevention and treatment of HCV infection.